Direct nitration of amines

DIRECT NITRATION OF AMINES 5.3.1 Nitration under acidic conditions... 

Unlike the direct nitration of amines under acidic conditions, nucleophilic nitration is an excellent route to both primary and secondary nitramines. In these reactions the amine or the conjugate base of the amine is used to attack a source of NO2. This source may be a nitrogen oxide, nitronium salt, cyanohydrin nitrate, alkyl nitrate ester or any other similar source of nitronium ion. 

Other reagents have been used for the direct nitration of amines under nonacidic conditions. Mandel reported the synthesis of methylnitramine, dimethylnitramine and diisopropy-Initramine from the reaction of nitryl fluoride with the parent amine. The presence of an excess of amine appears to be of prime importance given that other reports give the nitrosamine as a major by-product. 

At present there are four good methods for preparing secondary nitramines. They are the oxidation of nitrosamines by peroxytrifluoro-acetic acid (5), the chloride-ion catalyzed direct nitration of amines (3), the nitrolysis of dialkylamides with nitric acid (16), and the alkaline nitration of amines with acetone cyanohydrin nitrate (6). We have found that treating two equivalents of several secondary aliphatic amines... 

Nitration. Direct nitration of aromatic amines with nitric acid is not a satisfactory method, because the amino group is susceptible to oxidation. The amino group can be protected by acetylation, and the acetylamino derivative is then used in the nitration step. Nitration of acetanilide in sulfuric acid yields the 4-nitro compound that is hydroly2ed to -rutroaruline [100-01-6]. 

Direct nitration of dibenzothiophene occurs in the 2-position, while prior oxidation of the sulfur atom to either the sulfoxide or sulfone causes nitration to be directed to the 3-position. These two reactions form the starting point for the synthesis of most of the known derivatives of dibenzothiophene, which normally proceed via the derived amines. This has now been further illustrated by the synthesis of both 1-nitro- and 4-nitrodibenzothiophene from iV -derivatives of 2- and 3-aminodibenzo-thiophene, respectively, as described below. The synthesis of these two compounds thus completes the series of mononitrodibenzothiophenes. Unfortunately hopes of s3mthesizing nitrodibenzothiophenes via the chlorocyclohexanone route have been almost certainly ruled out by the failure to produce 2-nitrodibenzothiophene by this route (Section IV, A). 

The direct nitration of a primary amine to a nitramine with nitric acid or mixtures containing nitric acid is not possible due to the instability of the tautomeric isonitramine in strongly acidic solution (Equation 5.1). Secondary amines are far more stable under strongly acidic conditions and some of these can undergo electrophilic nitration with nitric acid in a dehydrating medium like acetic anhydride. 

More recently, Polish chemists have reported a synthesis of both aryl and aliphatic secondary nitramines by treating amine substrates with ethyl magnesium bromide followed by reaction with n-butyl nitrate (Equation 5.8). This method, which uses nonpolar solvents like hexane or benzene, has been used to synthesize aliphatic secondary nitramines, and At-nitro-A-methylanilines which otherwise undergo facile Bamberger rearrangement in the presence of acid. The direct nitration of At-unsubstituted arylamines usually requires the presence of an electron-withdrawing group. Reactions are retarded and yields are low for sterically hindered amines. 

The direct nitration of 2,6-diaminopyridine (168) with mixed acid yields 2,6-diamino-3,5-dinitropyridine (ANPy) (173). Oxidation of ANPy (173) with peroxyacetic acid yields ANPyO (174) (calculated VOD 7840 m/s, d = 1.88 g/crc ) C-Amination of ANPyO (174) with hydroxylamine hydrochloride in aqueous base yields the triamine (175), an impact insensitive explosive of high thermal stability. ... 

On the other hand, Elliott and his co-workers 4 maintain that the evidence for the nitro- structure is unsatisfactory, and that the p-nitro-dimethylaniline produced with dimethylaniline is a secondary product obtained either by oxidation of the nitroso-compound or by direct nitration of the amine. The addition of ethyl hydrogen sulphate to a solution of nitrosulphonic acid in sulphuric acid does not yield nitro -ethane. Elliott suggests that the crystalline acid is essentially the nitroso- form, ON. O. SO 2. OH, but that in the molten condition and in sulphuric acid solution this form is in equilibrium with another of yO ... 

The nitro group does not undergo migration of the naphthalene ring during the usual nitration procedures. Therefore, mono- and polynitration of naphthalene is similar to low temperature sulfonation, The nitronaphthalenes and some of their physical properties arc listed in fable 2. Many of these compounds are not accessible by direct nitration of naphthalene but are made by indirect methods, e.g nitrite displacement of diazonium halide groups in the presence of a copper catalysts, decarboxylation of nitronaphtbalcnccar-boxylic acids, or deamination of nitronaphthalene amines. They are nsed in the manufacture of chemicals, dye intermediates, and colorants for plastics. 

The directing influence of primary, secondary and tertiary amino groups is greatly weakened by the presence of large amounts of concentrated sulfuric acid. Hence, considerable quantities of the meta isomers are formed in the nitration of amines in concentrated sulfuric acid solution, and in the sulfonation of amines by concentrated sulfuric acid or oleum. 

Going from one of the most sensitive of the aromatic explosives to one of the very least sensitive, we have TATB (Figure 3.18). This is a new, very insensitive, high explosive that is finding broad use in nuclear weapons development. The extreme degree of insensitiveness boosts the safety in handling and in accident situations, which is so crucial in that particular application. It is made by direct nitration of 1,3,5-trichlorobenzene to 1,3,5-trichloro-2,4,6-trinitrobenzene. This, in turn, is then converted to the 1,3,5-triamino- by amine substitution of the three chlorine atoms. 

The nitramines are arrived at by various routes, but generally, the reaction is similar to the direct nitration of an organic amine with nitric acid. 

Methods of Preparation. Primary nitramines cannot be prepared by the direct nitration of primary amines. Because of their sensitivity toward acid, they probably do not survive in the strongly acidic environment of the nitration. They are generally made by alkaline hydrolysis of nitramides. 

Direct -nitration of secondary amines by nitric acid is possible only for weakly basic amines. The more basic amines can be nitrated under neutral conditions with reagents such as dinitrogen pentoxide and nitronium tetrafluoroborate, but nitrosamines are significant by-products. The nitrate ester CF3CMe20N02 has been recommended as a nonacidic nitrating agent for secondary amines which avoids the problem of contamination of the products by Af-nitrosamines piperidine and pyrrolidine were nitrated in yields of 75% and 72%, respectively. Amides and imides are efficiently A(-nitrated using ammonium nitrate in trifluoroacetic anhydride. ... 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

The nitro compounds which are products of direct nitration can undergo subsequent reduction yielding amines these amines can be converted into more versatile class of organic compounds as shown in Figure 1. This sequence provides a route to formation of dozens of aromatic compounds. 

Depending on the amine substrate and the nitrating conditions used, it is not uncommon for an intermediate nitramine to undergo direct rearrangement to the ring-nitrated product without prior isolation, in which case, the formation of the nitramine as an intermediate can only be postulated. Due to the high o-selectivity often observed with this type of reaction the o/p-ratio can be very different to that where the aromatic ring is directly nitrated. 

The replacement of amine and amide hydrogen with a nitro group via direct nitration is an important route to A-nitro functionality. However, the cleavage of other bonds is also important. In the case of C-N bond cleavage the process is known as nitrolysis and is an invaluable route to many energetic materials (Section 5.6). The nitrolysis of hexamine and the syntheses of the important explosives HMX and RDX are discussed in Section 5.15. This area of chemistry could easily demand a separate chapter of its own and is the most complex and diverse in the field of nitramine chemistry. 

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